Synergy between IgG and monoclonal IgM antibodies in antibody-dependent cell cytotoxicity.
Hybridoma-derived mouse monoclonal IgM anti-ox erythrocyte (ORBC) antibodies, which differed in their ability to exhibit complement-mediated cytotoxicity, direct agglutination and sensitization of indicator cells for detection of receptors for IgM on erythrocytes, failed to mediate antibody-dependent cell cytotoxicity (ADCC) by human K cells. Polyclonal rabbit IgM anti-ORBC antibodies were also incapable of mediating ADCC. However, one of the IgM monoclonal antibodies studied (clone 100) was highly efficient in synergizing with IgG in ADCC, especially when the E rosette-forming enriched fraction was used as a source of effector cells. This synergy was greater after overnight incubation of the lymphocytes and was partially blocked by human IgM. Since all the monoclonal antibodies studied bound efficiently to target ORBC as determined by the additional binding of 125I-labeled anti-k antibodies, the synergy did not appear to be due to a quantitative difference in the binding capacity of the antibodies. That the synergistic effect of purified clone 100 IgM was not due to heterophile IgG antibody was indicated by its sensitivity to reduction and lack of binding to a protein A column. The data are discussed in terms of the possible in vivo relevance of IgG-IgM synergy to immune protection, especially during the development of a primary antibody response when limiting amounts of specific IgG antibodies could be made more effective with the more abundant IgM antibodies.
D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity; D002417:Cattle; D002478:Cells, Cultured; D004912:Erythrocytes / Q000276:immunology; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D012397:Rosette Formation
D000906:Antibodies; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007075:Immunoglobulin M